Dual-barrel conductance micropipet as a new approach to the study of ionic crystal dissolution kinetics

A new approach to the study of ionic crystal dissolution kinetics is described, based on the use of a dual-barrel theta conductance micropipet. The solution in the pipet is undersaturated with respect to the crystal of interest, and when the meniscus at the end of the micropipet makes contact with a selected region of the crystal surface, dissolution occurs causing the solution composition to change. This is observed, with better than 1 ms time resolution, as a change in the ion conductance current, measured across a potential bias between an electrode in each barrel of the pipet. Key attributes of this new technique are: (i) dissolution can be targeted at a single crystal surface; (ii) multiple measurements can be made quickly and easily by moving the pipet to a new location on the surface; (iii) materials with a wide range of kinetics and solubilities are open to study because the duration of dissolution is controlled by the meniscus contact time; (iv) fast kinetics are readily amenable to study because of the intrinsically high mass transport rates within tapered micropipets; (v) the experimental geometry is well-defined, permitting finite element method modeling to allow quantitative analysis of experimental data. Herein, we study the dissolution of NaCl as an example system, with dissolution induced for just a few milliseconds, and estimate a first-order heterogeneous rate constant of 7.5 (±2.5) × 10–5 cm s–1 (equivalent surface dissolution flux ca. 0.5 μmol cm–2 s–1 into a completely undersaturated solution). Ionic crystals form a huge class of materials whose dissolution properties are of considerable interest, and we thus anticipate that this new localized microscale surface approach will have considerable applicability in the future

Phagocytosis in the retina promotes local insulin production in the eye

The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors (‘loss of function’) reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK (‘gain of function’) increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease

Beta-carotene affects gene expression in lungs of male and female Bcmo1−/− mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1−/− mice, which had, unlike wild-type (Bcmo1+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice